Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells.
Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells.
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DOI：
10.7150/ijbs.7357
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发表时间：
2014
影响因子：
9.2
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Li J;Dong L;Wei D;Wang X;Zhang S;Li H
本研究旨在探讨脂肪酸合成酶(FASN)在乳腺癌细胞上皮-间充质转化(EMT)中的作用。本研究以高表达丝裂原活化蛋白激酶5(MCF-7-MEK5)的MCF-7细胞和MCF-7细胞为研究对象。Mcf-7-MEK5细胞表现出稳定的EMT，其特征是波形蛋白表达增加，E-钙粘蛋白表达降低。用MCF-7或MCF-7-MEK5细胞原位注射建立体内动物模型。采用实时荧光定量聚合酶链式反应和免疫印迹技术检测FASN及其下游蛋白肝脏脂肪酸结合蛋白(L-FABP)和血管内皮生长因子/血管内皮生长因子受体-2(VEGFFR-2)在体外和体内模型(裸鼠肿瘤组织)中的表达。在MCF-7-MEK5细胞中，FASN的表达显著增加，并伴随着L-FABP和血管内皮生长因子/血管内皮生长因子受体-2表达的增加。蓝菌素可抑制MCF7-MEK5细胞的迁移和转分化，减少FASN的表达，并减少下游蛋白L-FABP、血管内皮生长因子和血管内皮生长因子受体-2的表达。MCF-7-MEK5细胞对蓝菌素的敏感性高于MCF-7细胞。免疫荧光显示FASN与血管内皮生长因子在细胞膜上的共定位增加，与L-FABP在MCF-7-MEK5细胞内的共定位增加。免疫组织化学进一步显示，肿瘤组织中FASN阳性细胞百分率的增加与L-FABP和血管内皮生长因子阳性细胞百分率的增加有关，蓝花菌素治疗可逆转这一作用。综上所述，我们的结果提示，FASN可能通过调节L-FABP、血管内皮生长因子和血管内皮细胞生长因子受体-2而参与EMT的发生。本研究为EMT有效抑制恶性细胞提供了理论依据和潜在策略。
This study aimed to investigate the role of fatty acid synthase (FASN) in the epithelial-mesenchymal transition (EMT) of breast cancer cells. MCF-7 cells and MCF-7 cells overexpressing mitogen-activated protein kinase 5 (MCF-7-MEK5) were used in this study. MCF-7-MEK5 cells showed stable EMT characterized by increased vimentin and decreased E-cadherin expression. An In vivo animal model was established using the orthotopic injection of MCF-7 or MCF-7-MEK5 cells. Real-time quantitative PCR and western blotting were used to detect the expression levels of FASN and its downstream proteins liver fatty acid-binding protein (L-FABP) and VEGF/VEGFR-2 in both in vitro and in vivo models (nude mouse tumor tissues). In MCF-7-MEK5 cells, significantly increased expression of FASN was associated with increased levels of L-FABP and VEGF/VEGFR-2. Cerulenin inhibited MCF-7-MEK5 cell migration and EMT, and reduced FASN expression and down-stream proteins L-FABP, VEGF, and VEGFR-2. MCF-7-MEK5 cells showed higher sensitivity to Cerulenin than MCF-7 cells. Immunofluorescence revealed an increase of co-localization of FASN with VEGF on the cell membrane and with L-FABP within MCF-7-MEK5 cells. Immunohistochemistry further showed that increased percentage of FASN-positive cells in the tumor tissue was associated with increased percentages of L-FABP- and VEGF-positive cells and the Cerulenin treatment could reverse the effect. Altogether, our results suggest that FASN is essential to EMT possibly through regulating L-FABP, VEGF and VEGFR-2. This study provides a theoretical basis and potential strategy for effective suppression of malignant cells with EMT.
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DOI：
10.1073/pnas.0403390101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Menendez, JA;Vellon, L;Lupu, R
通讯作者：
Lupu, R
影响因子：
7.5
作者：
Kapur, P;Rakheja, D;Hoang, MP
通讯作者：
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影响因子：
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作者：
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DOI：
10.1158/1541-7786.mcr-10-0201
发表时间：
2010-09
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
Selvendiran K;Ahmed S;Dayton A;Ravi Y;Kuppusamy ML;Bratasz A;Rivera BK;Kálai T;Hideg K;Kuppusamy P
通讯作者：
Kuppusamy P
影响因子：
2.5
作者：
Mercurio, Arthur M.;Lipscomb, Elizabeth A.;Bachelder, Robin E.
通讯作者：
Bachelder, Robin E.